Cadherins are the transmembrane component of the adherens junction, a structure that may appear at first glance to be a static structure. However, we know that cells must be able to adjust the strength of cellular adhesions in order to respond to their environment. We have shown that N-cadherin expression in oral squamous epithelial cells produces a cell with increased motility and invasion. Our hypothesis is that cells obtain signals when they make contact via cadherins and that the signals an oral squamous epithelial cell obtains by making contact via N-cadherin differs from the signal the same cell obtains by making contact via E-cadherin. The signals cells obtain through contact with one another allows them to modify their behavior. Our goal is to understand the signals epithelial cells receive through N-cadherin particularly when they inappropriately express this cadherin, and why these signals differ from those the same cell gets from E- cadherin. Signaling through cadherins has been difficult to study because there is no obvious way to "activate" the signal. Thus, for this proposal we have generated a unique activatible form of N-cadherin and propose to use this cadherin to investigate signals downstream of cadherin contact. A second goal is to determine if N-cadherin expression in oral epithelium is sufficient to produce a tumor or if it modifies the behavior of cells that are already tumor cells. To address this question we have generated a transgenic mouse model for oral cancer. Thus, our specific aims for this proposal are: 1) to understand cadherin-mediated cellular signaling; and 2) to understand the role N-cadherin plays in oral squamous cell carcinoma progression.